Bianchi N, Chiarabelli C, Borgatti M, Mischiati C, Fibach E, Gambari R
Department of Biochemistry and Molecular Biology, University of Ferrara, Italy.
Br J Haematol. 2001 Jun;113(4):951-61. doi: 10.1046/j.1365-2141.2001.02843.x.
Human leukaemic K562 cells can be induced in vitro to erythroid differentiation by a variety of chemical compounds, including haemin, butyric acid, 5-azacytidine, cytosine arabinoside, mithramycin and chromomycin, cisplatin and cisplatin analogues. Differentiation of K562 cells is associated with an increase of expression of embryo-fetal globin genes, such as the zeta-, epsilon- and gamma-globin genes. The K562 cell line has been proposed as a very useful in vitro model system to determine the therapeutic potential of new differentiating compounds as well as to study the molecular mechanism(s) regulating changes in the expression of embryonic and fetal human globin genes. Inducers of erythroid differentiation stimulating gamma-globin synthesis could be considered for possible use in the therapy of haematological diseases associated with a failure in the expression of normal beta-globin genes. We have analysed the effects of tallimustine and distamycin on cell growth and differentiation of K562 cells. The results demonstrated that tallimustine is a potent inducer, while distamycin is a weak inducer, of K562 cell erythroid differentiation. Erythroid differentiation was associated with an increase of accumulation of gamma-globin mRNA and of production of both haemoglobin (Hb) Gower 1 and Hb Portland. In addition, tallimustine-mediated erythroid induction occurred in the presence of activation of the apoptotic pathway. The reasons for proposing tallimustine as an inducer of gamma-globin gene expression are strongly sustained by the finding that this compound stimulates fetal haemoglobin production in human erythroid precursor cells from normal subjects.
人白血病K562细胞可在体外被多种化合物诱导向红系分化，这些化合物包括血红素、丁酸、5-氮杂胞苷、阿糖胞苷、光辉霉素和嗜癌霉素、顺铂及顺铂类似物。K562细胞的分化与胚胎 - 胎儿珠蛋白基因表达的增加有关，如ζ -、ε - 和γ - 珠蛋白基因。K562细胞系已被认为是一种非常有用的体外模型系统，可用于确定新的分化化合物的治疗潜力，以及研究调节人类胚胎和胎儿珠蛋白基因表达变化的分子机制。刺激γ - 珠蛋白合成的红系分化诱导剂可考虑用于治疗与正常β - 珠蛋白基因表达失败相关的血液疾病。我们分析了他莫司汀和偏端霉素对K562细胞生长和分化的影响。结果表明，他莫司汀是K562细胞红系分化的有效诱导剂，而偏端霉素是弱诱导剂。红系分化与γ - 珠蛋白mRNA积累的增加以及血红蛋白（Hb）戈尔1和Hb波特兰的产生增加有关。此外，他莫司汀介导的红系诱导发生在凋亡途径激活的情况下。将他莫司汀作为γ - 珠蛋白基因表达诱导剂的提议得到了有力支持，因为该化合物能刺激正常受试者人红系前体细胞中胎儿血红蛋白的产生。
